Analysis of slow and fast sleep spindle properties in Parkinson's disease - A comparative EEG study.

STUDY OBJECTIVES: Sleep disturbances and altered sleep macrostructure are common in Parkinson's disease (PD). Few studies have addressed the changes in sleep spindle (SS) properties in this movement disorder so far. SS seem to be fundamental of both sleep architecture and memory consolidation. The aim of our comparative study was to investigate the changes of SS characteristics in PD, and reveal the relationship between SS properties and cognitive function. METHODS: We investigated 20 PD patients and 18 age-matched controls. All participants underwent a 24-hour-long polygraphic EEG recording after extensive clinical investigation. We detected slow and fast SS properties automatically using individual adjusting method (IAM). The data were statistically evaluated. RESULTS: We found significantly lower fast spindle amplitude in PD comparing with controls. We did not find significant differences in SS densities, duration and oscillatory frequency between the groups. We detected significant positive correlation between fast SS amplitude and memory in PD, and between fast SS density and retrograde memory in controls. The total Addenbrooke's cognitive score correlated negatively with slow SS density and duration in controls. CONCLUSIONS: By the time clinical diagnosis of PD is established, the pathological process is already spreading. Changes in sleep macrostructure and SS properties might become a useful biomarker of the neurodegenerative process in PD. In addition, decreased fast SS amplitude might predict further cognitive deterioration and indicate early involvement of corresponding cortical area. Our study results strengthen the importance of EEG examination in PD, and the use of IAM method in SS analysis.

REM sleep, REM parasomnias, REM sleep behaviour disorder.

We review the literature on REM parasomnias, and their the underlying mechanisms. Several REM parasomnias are consistent with sleep dissociations, where certain elements of the REM sleep pattern emerge in an inadequate time (sleep paralysis, hypnagogic hallucinations and cataplexy) or are absent/partial in their normal REM sleep time (REM sleep without atonia, underlying REM sleep behavior disorder). The rest of REM parasomnias (sleep related painful erection, catathrenia) may have other still unclear mechanisms. REM parasomnias deserve attention, because in addition to disturbing sleep and causing injuries, they may shed light on REM sleep functions as well as the heterogeneous etiologies of parasomnias. One of them, REM sleep behavior disorder has special importance as a warning sign of evolving neurodegenerative conditions mainly synucleinopathies (some cases synucleinopathies themselves) and it is a model parasomnia revealing that parasomnias may have by autoimmune, iatrogenic and even psychosomatic etiologies.

Sleep alterations are related to cognitive symptoms in Parkinson's disease: A 24-hour ambulatory polygraphic EEG study.

BACKGROUND: Sleep disorders are frequent and early non-motor symptoms of Parkinson's disease (PD). As a consequence of histopathological changes, the regulation of rapid eye movement (REM) sleep is affected in PD causing REM sleep behaviour disorder in about half of the patients. Considering the well-known role of sleep in memory formation processes, our aim was to investigate the relationship between sleep alterations and cognitive performance to elucidate the possible association between sleep, and especially REM sleep changes and cognitive dysfunction in PD. METHODS: We investigated 25 PD patients and 20 healthy controls. All participants underwent a 24-hour-long 19-channel polygraphic EEG recording, neurological, neuroimaging and neuropsychological examination. The visually analysed sleep-EEG and neuropsychological data were statistically evaluated. RESULTS: The intergroup analysis showed significant decrease of REM and N3, but increase of N2 sleep ratio, and significantly lower scores in the verbal fluency in PD compared to healthy controls. While we found significant negative correlation between verbal fluency and REM-sleep in the whole sample, we observed a marginal significant correlation between phonemic fluency and REM sleep in the PD group. CONCLUSION: The negative correlation between verbal fluency performance and REM sleep duration suggests the role of decreased REM sleep in cognitive dysfunction in PD. The early involvement of REM sleep regulation with parallel executive dysfunction in PD emphasise the important role of REM sleep deterioration in the neurodegenerative process of PD.

The complex presentation of carcinomatous meningitis / A meningitis carcinomatosa komplex megjelenése.

Összefoglaló. Az emlotumor miatt kezelt, majd gondozott beteget - több tünetmentes év után - fejfájás, szédülés, ataxia, megváltozott, furcsa viselkedés, emlékezetzavar és dezorientáció miatt neurológiai, majd belgyógyászati osztályokon vizsgálták. Az alapos kivizsgálás ellenére a tüneteit magyarázó organikus eltérést nem igazoltak, ugyanakkor már a kezdetektol felmerült a szomatizációs tünetképzés lehetosége, ezért pszichiátriai osztályos felvételére került sor. Az elvégzett vizsgálatok, illetve a klinikai kép regresszív állapotot valószínusítettek. Terápiás próbálkozásaink ellenére a páciens állapota romlott, végül a megismételt neurológiai vizsgálatok meningitis carcinomatosát igazoltak. Az esettel szemléltetni kívánjuk, hogy a beteg premorbid muködési nívója, személyiségstruktúrája hogyan képes befolyásolni az ellátószemélyzetet, milyen külso és belso konfliktusokat válthat ki. A diagnózishoz vezeto folyamat bemutatásával fel kívánjuk hívni a figyelmet az interdiszciplináris együttmuködés fontosságára. Orv Hetil. 2021; 162(43): 1744-1748. Summary. Our patient with known breast cancer in her past medical history was hospitalized - after several asymptomatic years - for headache, dizziness, ataxia, changed behaviour and disorientation. Thorough internal and neurologic investigations did not find any disease underlying her symptoms, therefore the possibility of somatization disorder was raised. Despite lege artis therapeutic interventions carried out on the psychiatry ward, the patient's condition deteriorated and repeated neurological examinations eventually revealed carcinomatous meningitis. With this case, we would like to illustrate how the patient's premorbid function level and personality features might influence the attitude and opinion of the health care personnel, and what kind of external and internal conflicts might be triggered. By presenting the complexity of the diagnostic work-up, we would like to emphasize the importance of interdisciplinary cooperation in the interest of our patients. Orv Hetil. 2021; 162(43): 1744-1748.

Subclinical epileptiform activity accelerates the progression of Alzheimer's disease: A long-term EEG study.

OBJECTIVE: While many studies suggest that patients with Alzheimer's disease have a higher chance for developing epileptic seizures, only a few studies are available examining independent epileptic discharges. The major aims of our study was to determine the prevalence of subclinical epileptiform activity (SEA) in AD compared to healthy elderly controls with the hypothesis that SEA is more frequent in AD than in cognitively normal individuals. Another aim was to analyze the effect of baseline SEA captured with electroencephalography on the progression of the disease with longitudinal cognitive testing. METHODS: We investigated 52 Alzheimer patients with no history of epileptic seizures and 20 healthy individuals. All participants underwent a 24-hour electroencephalography, neurology, neuroimaging and neuropsychology examination. Two independent raters analyzed visually the electroencephalograms and both raters were blind to the diagnoses. Thirty-eight Alzheimer patients were enrolled in a 3-year long prospective follow-up study with yearly repeated cognitive evaluation. RESULTS: Subclinical epileptiform discharges were recorded significantly (p:0.018) more frequently in Alzheimer patients (54%) than in healthy elderly (25%). Epileptiform discharges were associated with lower performance scores in memory. Alzheimer patients with spikes showed 1.5-times faster decline in global cognitive scores than patients without (p < 0.001). The decline in cognitive performance scores showed a significant positive correlation with spike frequency (r:+0.664; p < 0.001). CONCLUSIONS: Subclinical epileptiform activity occurs in half of Alzheimer patients who have never suffered epileptic seizures. Alzheimer patients with subclinical epileptiform activity showed accelerated cognitive decline with a strong relation to the frequency and spatial distribution (left temporal) of spikes. SIGNIFICANCE: Our findings suggest the prominent role of epileptiform discharges in the pathomechanism of Alzheimer's disease which might serve as potential therapeutic target.

Progress in elucidating the pathophysiological basis of nonrapid eye movement parasomnias: not yet informing therapeutic strategies.

Nonrapid eye movement (NREM) or arousal parasomnias are prevalent conditions in children and young adults, apparently provoked by any medical, physical, mental, or pharmacologic/toxic agent disturbing normal biorhythm and causing sleep fragmentation or abundant amount of slow wave sleep. The nadir and the ascending slope of the first sleep cycle of night sleep are the typical periods when NREM parasomnias, especially sleepwalking may occur on sleep-microstructural level; microarousals are the typical moments allowing NREM parasomnias. While sleep-disturbing factors have a clear precipitating effect, a genetic predisposition appears necessary in most cases. A candidate gene for sleepwalking has been identified on chromosome 20q12-q13.12 in one sleepwalking family. NREM parasomnias have a genetic and clinical link with nocturnal-frontal lobe epilepsies; possibly through an abnormality of the acetylcholine-related sleep-control system. The association of NREM parasomnias with the human leukocyte antigen system might be the sign of an autoimmune background to be further clarified. In the treatment of arousal parasomnias, the main tools are adequate sleep hygiene and the management of underlying conditions. Their pharmacotherapy has remained unresolved; the best options are clonazepam and some of the antidepressants, while a psychotherapy approach is also justified.